Immunohistochemical Localization of Adhesion Molecules - Adhesion Molecules - page 29

ZO-2 was dif usely expressed in the proximal tubules with weak cell border staining
but was highly expressed at cell borders from Henle's loop to collecting ducts. In
mouse kidney, claudins-1 and -2 are expressed in the Bowman's capsule, while
claudins-2, -10 and -11 are found in proximal tubules (Kiuchi-Saishin et al. 2002).
In the thin descending limb of Henle, claudin-2 is expressed and claudins-3, -4
and -8 are localized to the thin ascending limb of Henle. Claudins-3, -10, -11 and
-16 are expressed in the thick ascending limb of Henle, while claudins-3 and -8
are present in the distal tubule and claudins-3, -4 and -8 in the collecting duct. It
is postulated that claudin-2 might form a 'leakier' tight junction than claudin-3,
based on localization along the nephron. h e i nding that enforced expression
of claudin-2 is associated with the conversion from 'tight' to 'leaky' junctions in
MDCK cells supports this hypothesis (Furuse et al. 2001). However, the higher
expression of occludin, ZO-1, and ZO-2 in distal tubules than in proximal tubules
likely also contributes to dif erences in the 'strength' of tight junctions along the
nephron.
In adult mouse kidney, E-cadherin is detected everywhere but the initial
segment where the proximal tubule joins Bowman's capsule (Piepenhagen et al.
1995). h is pattern of expression contrasts with that of adult human kidney, where
E-cadherin is not detected in the proximal tubule (Nouwen et al. 1993). N-cadherin
is expressed in the proximal, but not distal, tubules (Nouwen et al. 1993). Given
that E- and N-cadherin are highly homologous, the functional relevance of the
localization of N-cadherin in the proximal tubules and E-cadherin in the distal
tubules is unclear. α- and β-catenin are expressed in all nephron segments
(adult mouse), while γ-catenin is detected only in the distal part of the nephron
(Piepenhagen and Nelson 1995).
Cancer
Immunohistochemistry plays a critical role in the detection and progression of
some cancers. In malignant tumors, intracellular adhesion decreases because
of the loss of E-cadherin and the cells change from a stationary epithelial type
cell with cell-to-cell adhesion to a mesenchymal cell with increased tumor cell
motility and invasive properties necessary for distant metastases (Guarino et al.
2007). h is mesenchymal cell type is reminiscent of early migratory embryological
mesenchymal tissue. Stationary epithelial cells thus modulate their phenotype
by progressively weakening their cell-cell connections and acquire migratory
mesenchymal-like properties with the ability to migrate as individual cells
(Guarino et al. 2007). h is epithelial-mesenchymal transition or 'cadherin switch'
is a phenomenon in which N-cadherin is overexpressed with the loss of E-cadherin
and has been associated with advancing stages of breast, prostate and liver cancer
(Chetty et al. 2008) ( Fig. 8 ). h e loss of cell-cell contact is not the only consequence
of the 'cadherin switch, but E-cadherin is known to be intimately associated with